Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy

NCT00225758 | Terminated Phase 2 Results DMC

• 1 other identifier: D-0520
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present. Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis. Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined. Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; endocrine therapy; drug resistance; lapatinib; epidermal growth factor receptor

Outcome Measures

Primary Outcomes (2)

• Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib.

  A response is defined as stable disease or better at 26 weeks. Twenty two patients are evaluable for response

  26 weeks

• Progression-free Survival

  Progression-free survival is the time between date on study and progression based on RECIST criteria.

  Up to 575 days

Secondary Outcomes (3)

• Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer

  26 weeks

• Determine Changes in Activation of Tumor Cell ERK and Akt, as Between the Hormonal Agent and Lapatinib Contributes to the Molecular Pharmacodynamic Effect Postulated Above.

  4 weeks

• Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib

  14 weeks

Study Arms (1)

1

EXPERIMENTAL

Subjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer.

Drug: Lapatinib

Interventions

Lapatinib DRUG

1500 mg po daily for 26 weeks or longer

Also known as: Tykerb

1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically proven metastatic breast cancer.
• Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.
• Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.
• Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.
• Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.
• Patients must have stopped fulvestrant at least four weeks prior and other endocrine therapy at least two weeks prior to enrollment on study.
• Patients must have either measurable disease or at least one evaluable bone lesion that has not been irradiated. Measurable disease is not necessary.
• Estimated life expectancy of at least 6 months.
• ECOG performance status 0-2.
• Adequate hematologic, hepatic, and renal function.
• Patients must be post-menopausal, or they must be practicing either abstinence or an adequate method of contraception, or their sexual partner must be sterile.
• All patients must be able to swallow, retain, and absorb oral medications.
• All patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.

You may not qualify if:

• Patients may not have received an investigational agent within the prior four weeks.
• Patients may not have received trastuzumab within three weeks of study entry.
• Patients may not have had major surgery within the prior two weeks.
• Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.
• Patients may not have a left ventricular ejection fraction \< 40% based on MUGA or echocardiogram.
• Patients may not have uncontrolled brain metastases or leptomeningeal disease.
• Patients may not have rapidly progressive visceral metastases.
• Patients may not have a serious illness or conditions including clinically significant cardiac disease, angina pectoris, serious psychiatric disorder, or an active infection.
• Patients may not be receiving concurrent medications (listed in the protocol) which may interact with lapatinib during treatment with lapatinib.

Sponsors & Collaborators

• Gary Schwartz: lead
• University of Colorado, Denver: collaborator
• North Shore University Hospital: collaborator

Study Sites (3)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

North Shore University Hospital

Lake Success, New York, 11042, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gary N. Schwartz, MD
• Organization: Dartmouth-Hitchcock Medical Center

gary.n.schwartz@hitchcock.org

(603) 653-6181

Study Officials

• Gary N Schwartz, MD

  Norris Cotton Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: September 22, 2005
• First Posted: September 26, 2005
• Study Start: January 1, 2006
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: July 27, 2018
• Results First Posted: July 27, 2018

Record last verified: 2018-07

Locations

US (3)